The purpose of this program project grant is to carry forward MIDUS, a national survey (N= 7,189), conducted in 1994/95 by the MacArthur Midlife Research Network. The sample included adults aged 25 to 74, as well as twins and siblings. Conceived by a multidisciplinary team, the study investigated the role of behavioral, psychological, and social factors in accounting for age-related variations in health and illness. MIDUS II will add a second wave to the study, approximately 9-10 years later. In addition, it will include a sample of African Americans in Milwaukee, WI (N= 400). Project 1 data collection will include a repeat assessment of the original MIDUS telephone interview and self-administered questionnaire. These instruments will be augmented to include new assessments of cognitive functioning, optimism and coping, stressful events, and caregiving. Built around the Project 1 data collection are five projects, each adding significant strengths to the overall agenda. Project 2 will use diary techniques to assess daily stressors in a subsample of MIDUS respondents (including twins) and their effects on health and well being. Project 3 will focus on cognitive functioning and its connection to other psychological factors, as well as health outcomes and will include in-depth laboratory analyses with a Boston over-sample. Project 4 will collect biological data on a subsample of MIDUS respondents located in three geographic regions, with a focus on multiple indicators of physiological wear and tear that will be linked with multi-domain psychosocial experience. The biological data collection will include laboratory challenge studies (both cognitive and orthostatic), with accompanying assessments of salivary cortisol, blood pressure and heart-rate variability. Project 5 will focus on the central circuitry of emotion (affective neuroscience) and will include EEG measures of cerebral activation asymmetry and emotion-modulated startle. These measures have been previously linked to dispositional affect, depression, recovery from stressful events, and selected biomarkers. MIDUS affords the opportunity to investigate such relationships in a sociodemographically diverse sample with wide age ranges and comprehensive biomarkers. Five scientific cores surround these projects (Coordination, Psychosocial Measures, Biological Measures, Statistics, and Pilot Studies). Collectively, the scientific agenda represents a multi-level, multidisciplinary approach to understanding life course pathways to health and illness. The team of investigators has an outstanding record of past success working together to advance the frontiers of integrative science. All projects and cores include detailed responses to feedback received in the prior round of reviews.